The purpose of the proposed research is to study a means of treating infants and children who have defects of the enzymes required for urea synthesis (other than argininosuccinic aciduria), by minimizing the requirements for waste nitrogen excretion by supplementing a low protein diet with nitrogen-free analogues of essential amino acids. Infants with partial or complete defects of one of these enzymes, identified by pediatricians elsewhere as well as by Johns Hopkins Hospital personnel, will be maintained on a low-protein regimen in which essential amino acid requirements are met by a mixture of essential amino acids and their nitrogen-free analogues, produced at Johns Hopkins and sent regularly to the primary physicians. Dosage of individual components and protein intake will be modified continually so as to optimize physical growth, neurodevelopment, and biochemical parameters. Attempts will be made, without jeopardizing the fragile clinical status of these infants, to determine (1) the optimal protein intake and plasma amino acid levels that will permit normal physical growth and neurodevelopment without increasing the risk of hyperammonemic episodes; (2) the optimal arginine intake; (3) whether S- or RS-alpha-keto-beta-methylvalerate is preferable; and (4) whether more palatable supplements can be designed by using mixed salts of arginine, lysine, and histidine with branched-chain ketoacids and/or phenylpyruvate.